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The normal QRS duration is <100 ms. Right bundle branch block usually has a QRS duration in the 110- to 150-ms range with particular prolongation of the terminal portion of the conduction pattern as seen most prominently in leads I and V1, and left bundle branch block (LBBB) has a QRS duration mostly in the 130- to 180-ms range. Of course, there are exceptions to these ranges for specific bundle branch block patterns for a variety of reasons related to factors involved in complex aspects of intraventricular conduction. Heart failure with cardiac enlargement plays an important role, leading to dysregulation of gap junctions with associated electrical uncoupling that can prolong the QRS duration (1). The combination of LBBB and/or heart failure dysregulation with electrical uncoupling can result in very wide QRS complexes >180 ms. In the paper by Sundaram et al. (2) in this issue of the Journal, the authors have investigated the efficacy of cardiac resynchronization therapy (CRT) in patients with QRS durations of ≥180 ms whether associated or not associated with LBBB.

Several studies have substantiated the reduction in mortality with CRT in patients with heart failure (3–5). In the randomized MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy) trial involving 1800 patients with an ejection fraction of ≤30%, CRT with an implantable cardioverter defibrillator (ICD) (CRT-D) was associated with a significant reduction in heart failure compared with ICD alone during a follow-up averaging 2.4 years (6). In further follow-up of the initial MADIT-CRT study (7), CRT benefit was related exclusively to patients with LBBB, but not to patients with non-LBBB patterns. Subsequent analysis of the MADIT-CRT patients revealed that a QRS duration of ≥180 ms was present in 21.9% of patients with LBBB, but only 4.5% of patients without LBBB. A long-term, 7-year follow-up of the MADIT-CRT patients revealed that CRT was associated with survival benefit in those with LBBB but not in those without LBBB (8).

Sundaram et al. (2) determined the outcome of death and heart failure hospitalization in patients with CRT-D in very wide QRS duration (≥180 ms) with LBBB versus without LBBB (2). Records were obtained for 12,480 patients with CRT-D who were propensity matched to 12,478 ICD patients using the Iowa Foundation for Medicare registry during the years 2005 and 2006. Improvements in both survival and heart failure hospitalization with CRT-D were greatest in patients with a QRS duration of ≥180 ms with or without LBBB, whereas patients with QRS duration of 150 to 179 ms had no improvement in survival with CRT-D in the case of patients without LBBB, and only a modest improvement in the case of those with LBBB. The authors suggest that, in heart failure patients, a very wide QRS duration is possibly a marker of advanced electrical and myocardial remodeling and that the pathophysiologic progression of disease can be partially reversed with CRT-D, irrespective of BBB morphology, a reasonable interpretation. Although retrospective studies have limitations, the study by Sundaram et al. (2) involved a large patient population with propensity matching, excellent biostatistical analyses, and long-term follow-up such that the findings may be valid. However, it would have been informative to have follow-up electrocardiograms and echocardiograms that were not available in the registry.

What are the clinical implications of the study from Sundaram et al. (2)? They suggest that a very wide QRS duration should be part of the clinical decision making for CRT-D implantation, while also taking LBBB status into consideration. In patients without LBBB and a very wide QRS of ≥180 ms, CRT-D might be beneficial to improve outcomes of heart failure or death.

Nevertheless, reported outcomes of CRT-D in heart failure patients without LBBB remain controversial. In our recent substudy of the MADIT-CRT trial, heart failure patients without LBBB and a prolonged PR interval derived sustained long-term clinical benefit from CRT-D implantation with reductions in heart failure or death compared with ICD-only therapy (9). In our studies, we have not seen differences in outcomes in patients without LBBB by QRS duration (7,9). Although current guidelines suggest implantation of a CRT-D in patients without LBBB with QRS duration of >150 ms (10), Sudaram et al. suggest using a higher QRS cutoff based on their findings. Although their study is intriguing, it is not a randomized clinical trial to provide us with a clear answer to this relevant clinical question. Taken altogether, response to CRT-D in the subcohort without LBBB is not currently well understood and needs further research. Future randomized studies are warranted to evaluate response to CRT-D in patients without LBBB electrocardiogram morphology.

Over the past few years, there has been a meaningful advancement in pharmacological as well as ICD and CRT-D device therapy for heart failure and associated conduction disturbances. Ivabradine works by slowing the heart rate even in patients on beta-blockers (11), and eplerenone is a selective mineralocorticoid receptor antagonist (12); both drugs have been incorporated into U.S. and European heart failure guidelines. Programming of ICD devices to longer detection intervals and higher rate cutoffs have reduced inappropriate ICD discharges (13). We reported from MADIT-CRT that the benefit from CRT-D is confined to LBBB (7) and to patients without LBBB with prolonged PR interval (9,14). Additional drugs and devices that are currently under investigation should further improve management of patients with advanced heart failure.

Footnotes

↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

Drs. Moss and Kutyifa have a research grant funded by Boston Scientific, Inc.

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